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Vala Nears End of Grant to Develop hESC Differentiation Assay

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Vala Sciences has recently entered the final year of a three-year collaborative grant with the Burnham Institute to develop live-cell and high-content screening assays to quantify how stem cells differentiate into cardiomyocytes.
 
The award for fiscal 2008, administered by the National Heart, Lung, and Blood Institute as in previous years, is for $628,906.
 
A Vala Sciences official told CBA News this week that the basic assay technology being developed will measure calcium response in live cardiomyocytes. The grant will enable the shop to use the technology to characterize how human embryonic stem cells differentiate into cardiomyocytes. 
 
“This is a way to monitor the [cardiomyocytes’] development in a culture dish, and characterize how the hESCs are differentiating, in addition to determining what kind of cells they are differentiating into,” said Jeffrey Price, president and CEO of Vala.
 
The assays will measure calcium transients in cells cultured in 96-well plates so that “we could screen 96 different compounds for their ability to stimulate the differentiation of hESCs into cardiomyocytes,” said Patrick McDonough, vice president of biological studies and the principal investigator on the grant.
 
The endpoint would be, for example, at the end of several days’ exposure, to put the cells on the apparatus that Vala is developing, and then measure the calcium transients that can be electrically stimulated in the cells.
 
Mature cardiomyocytes respond to electrical stimulation with increased calcium transients. “We are essentially creating video clips of each well, and then looking at each individual cell within the field of view and quantifying their response to the electrical stimulation, ie, whether or not they generate a calcium transient, and get the kinetics from it,” McDonough told CBA News.
 
This device is relevant to drug discovery in two ways: Researchers are still trying to produce cardiomyocytes from hESCs, so they are always looking for compounds that will increase the yield from the differentiation protocols, said McDonough. Discovering a chemical that will positively influence that yield will be useful, because these cells could then be transplanted into a failing heart and provide a therapy.
 
A second, but related, application is to put mature cardiac cells in the device and test compounds for cardiotoxicity. 
 

“This is a way to monitor the cells’ development in a culture dish, and characterize how the cells are differentiating, in addition to determining what kind of cells they are developing into.”

Vala already has a prototype device that it is testing in collaboration with Mark Mercola’s team at Burnham. “We are still working out some of the details on the hardware,” said McDonough. Although the device is currently functioning, the researchers are looking at making improvements to some of the electrodes to speed up how fast the assay can be performed.
 
The investigators are currently evaluating compounds, according to McDonough. “We have done tests on compounds that alter the way that cardiomyocytes beat and contract, and we can measure that with a calcium wave,” he said. 
 
McDonough did not mention what compounds were tested, or for what indication the tested compounds would be used.
 
McDonough added that although Vala does not know when a commercial device based on his group’s assay may be released, “it should be relatively soon.”  
 
The company is also considering marketing the technology as a device or as a service. “It may be faster to market it as a service to drug discovery companies,” said Casey Laris, Vala’s director of marketing.   
 
CyteSeeing
 
In terms of high-content imaging software, Vala currently offers a panel of three products. The CyteSeer ViewRNA facilitates in situ mRNA analysis from microscope images on slides and well plates. “We have this product in a few customers’ hands already, and we are actively trying to ramp up our efforts there,” said Laris.
 
The company also offers the CyteSeer, a general high-content analysis tool that can be used for lipids, cadherins, β-catenin, and perilipin. CyteSeer Pro extends this tool with plug-in support.
 
According to the company’s website, the CyteSeer software works with any operating system — Windows Vista or XP, Linux, and Mac OS X — and an array of instruments from major vendors, including Cellomics, BD, Beckman Coulter, Evotec, and GE Healthcare.
 
Vala did not comment on the value of the market for its software.
 
Three years ago, big, high-content systems providers were rapidly acquiring software vendors (see CBA News, 7/18/05). Vala, for its part, has managed to remain independent.
 
Vala Sciences’ approach is to create the open CyteSeer software tool set, said McDonough. “The way we envision that is to broadly collaborate with the vendors that are out there, and we think that there is a great role for someone who can do that, and provide tools that can cross multiple platforms, are hardware-independent, and can meet the needs of multiple instruments and multiple customers.”
 
Vala is also involved in several other grants. For example, the company has grants to develop high-throughput imaging assays to analyze the formation of fat in liver disease, both in adipocytes and in hepatocytes. These efforts are under the auspices of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Drug Abuse, respectively.
 
Collaborators on these projects are Zen-Bio, Baylor College of Medicine, and the Burnham Institute.
 
The company also has a grant for analyzing the formation of lipid in skeletal muscle and skeletal muscle fiber cross sections. This project, funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, is being done in collaboration with the University of Indiana.
 
Grants such as these create “a nice set of assay-development resources for us over the next several years,” said Price. The company plans to use these resources to help it expand both its panel of software and its panel of kits, and “reach customers who are performing challenging high-content imaging assays, both in academic labs and in biotech and pharmaceutical companies.”

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